Real-world heterogeneity in the prognostic value of pre-transplant flow cytometry measurable residual disease in acute myeloid leukemia in first complete remission: CIBMTR analysis

In this real-world, large, observational study from the Center for International Blood and Marrow Transplant Research (CIBMTR), we examined the association between pre-transplant measurable residual disease (MRD) detected by multiparameter flow cytometry (MFC) test results and outcomes after allogeneic hematopoietic cell transplantation (alloHCT) in patients with acute myeloid leukemia (AML) in first complete remission (CR1). We included 2,544 patients who underwent transplant during 2013-2019; 11% had detectable MRD prior to alloHCT. Patients' median age was 58 years. Among MRD-negative and MRD-positive groups, 48% vs 52% received myeloablative conditioning, and 37% vs 29% had matched unrelated donors, respectively. The 1-year cumulative incidence of relapse was 35% in the MRD-positive group and 25% in the MRD-negative group (P < .001). MRD positivity was associated with inferior overall survival (hazard ratio [HR], 1.27; 95% CI, 1.06-1.51; P = .009) and disease-free survival (HR, 1.31; 95% CI, 1.11-1.53; P = .001), and increased relapse risk (HR, 1.42; 95% CI, 1.17-1.72; P < .001), but not with non-relapse mortality. Notably, patients with pre-alloHCT MRD negativity remained at high risk of relapse, underscoring the limited prognostic utility of registryreported MFC-MRD testing due to variability in methods and thresholds. Survival analyses across the 12 largest centers demonstrated substantial variability in the prognostic impact of MRD. These findings underscore that although pre-alloHCT MRD by MFC remains a clinically relevant prognostic biomarker, its reliability is contingent upon methodological standardization across centers. These findings highlight the need for standardized MRD assessment to improve risk stratification in AML.